Spontaneous Self-Assembly of Metal-Organic Cationic Nanocages to Form Monodisperse Hollow Vesicles in Dilute Solutions Dong Li, Jie Zhang, Kai Landskron,* and Tianbo Liu* Department of Chemistry, Lehigh UniVersity, Bethlehem, PennsylVania, 18015 Received December 4, 2007; E-mail: kal205@lehigh.edu; liu@lehigh.edu Metal-organic nanocages are an extensive class of giant, porous molecules that formed by small organic ligands and metal ions. Their shape, size, charge, and composition can be rationally designed by the choice of metal ion and organic ligands. 1-3 Due to their molecular nature, the cages have precisely defined cage windows, or pore-openings, making the cages accessible to guest molecules. 1-3 Therefore, the metal-organic cages not only are appealing by their aesthetic shape but also show a distinguished host-guest chemistry that has recently emerged. Beyond their fascinating properties as nanoscaled molecules, herein we report the spontaneous self-assembly of highly water soluble metal-organic nanocages to form hollow, spherical, vesicle- like structures with tunable sizes. This is a completely new phenomenon observed for metal-organic nanocages (Figure 1). The commercially available (Wako) Pd 6 L 4 (NO 3 ) 12 {Pd ) eth- ylenediamine palladium(II), L ) 2,4,6-tris(4-pyridyl)-triazine} metal-organic nanocage (Figure 1), first reported by Fujita, 4 was used for this study, which has an octahedral shape and a diameter of ∼2 nm. 4 In pure water each nanocage carries 12 positive charges attributed to 6 Pd 2+ ions, after releasing 12 NO 3 - counterions into solution. The Pd 6 L 4 (NO 3 ) 12 solutions were studied by dynamic and static light scattering (DLS and SLS) techniques. In a pure aqueous solution, very low scattered intensity was collected by SLS after several weeks, indicating that there was no large structure forming in solution; i.e., the cages existed as discrete macrocations. This is due to the high charge density of the nanocages and not a surprise for highly soluble ions. However, when different amounts of acetone were added into the aqueous solutions of nanocages, a significant and continuous increase of the total scattered intensity from SLS was observed, suggesting the formation of much larger structures. The nanocages are still quite soluble in such water/acetone mixtures (up to 75 v% acetone at 0.20 mg/mL) and form clear, stable, homogeneous solutions. Therefore, the growth of the scattered intensity is not due to the aggregation of insoluble species but a slow self- association process of individual cages. As revealed in Figure 2, the peaks obtained by Constrained Regularization (CONTIN) analysis 5 from DLS studies of a 0.20 mg/mL nanocage solution with 22 v% acetone are attributed to supramolecular structures which are dominant in solution and have narrow size distributions. The average hydrodynamic radius (R h ) of the large structures does not change with time, indicating that such supramolecular structures have preferred curvatures in solution. Besides, in a 0.06 mg/mL nanocage solution containing 40 v% acetone, the average R h is 38 ( 1.0 nm measured at a 90° scattering angle. Extrapolating the R h values to a 0° scattering angle results in an R h,0 of 40.5 nm. SLS measurements performed on the same solutions indicate that the average radius of gyration (R g ) of the supramolecular structures is 40.8 ( 0.8 nm. Therefore, the ratio R g /R h is very close to 1. For spherical objects (TEM evidence provided in Figure 3), if they are solid in nature, the general rule of R g /R h ) 0.77 holds. When R g /R h ≈ 1, it implies that the mass of the particle is almost entirely distributed on its surface. Accordingly, it serves as strong evidence that the assemblies formed by Pd 6 L 4 cationic nanocages observed at this circumstance have a hollow, vesicle-like structure. TEM studies also clearly show the presence of uniform, hollow, vesicle-like structures formed by Pd 6 L 4 cationic nanocages, with the average radius of ∼40 nm in 40 v% acetone solution (Figure Figure 1. (A) Three-dimensional structure of a single metal-organic nanocage molecule. (B) The supramolecular blackberry type structure determined by laser light scattering measurements and TEM. Figure 2. Hydrodynamic radius (Rh) distributions of 0.20 mg/mL Pd6L4 cationic nanocage aqueous solution with 22 v% acetone (Ac) after 1, 5, 10, 21, and 30 days. The scattering angle is set at 90°. Figure 3. TEM studies of a 0.06 mg/mL Pd6L4 cationic nanocage aqueous solution containing 40 v% acetone. (A) 38-40 nm radius vesicles; (B) a zoom-in image of A; (C) a comprehensive view of burst and intact vesicles which show soft, membrane-like property. Published on Web 03/11/2008 4226 9 J. AM. CHEM. SOC. 2008, 130, 4226-4227 10.1021/ja710820a CCC: $40.75 © 2008 American Chemical Society